title: Phosphatidylinositol 3-monophosphate is involved in toxoplasma apicoplast biogenesis.
abstract: Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs.
authors.affiliation: UMR 5235 CNRS, Université Montpellier 1 & 2, Montpellier, France.
authors.forename: Lina
authors.initials: L
authors.lastname: Tawk
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.forename: Philippe
authors.initials: P
authors.lastname: Montcourrier
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Chicanne
authors.forename: Fabrice
authors.initials: F
authors.lastname: Merezegue
authors.forename: Véronique
authors.initials: V
authors.lastname: Richard
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.forename: Markus
authors.initials: M
authors.lastname: Meissner
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Vial
authors.forename: Christian
authors.initials: C
authors.lastname: Roy
authors.forename: Kai
authors.initials: K
authors.lastname: Wengelnik
authors.forename: Maryse
authors.initials: M
authors.lastname: Lebrun
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D016782:Apicomplexa; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D052816:Foreskin / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D001678:Organelle Biogenesis; D015388:Organelles / Q000378:metabolism* / Q000469:parasitology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000378:metabolism* / Q000469:parasitology
chemical_list: D018129:Phosphatidylinositol Phosphates; C485184:enhanced green fluorescent protein; C055525:phosphatidylinositol 3-phosphate; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases